ClinVar Miner

Submissions for variant NM_006432.5(NPC2):c.422G>A (p.Trp141Ter)

dbSNP: rs1555345616
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668992 SCV000793681 likely pathogenic Niemann-Pick disease, type C2 2017-08-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000668992 SCV002126627 pathogenic Niemann-Pick disease, type C2 2021-04-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the NPC2 protein. Other variant(s) that disrupt this region (p.Gln146*) have been determined to be pathogenic (PMID: 16126423, 32138288). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This sequence change creates a premature translational stop signal (p.Trp141*) in the NPC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the NPC2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NPC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 553522). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies.

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